1,003 research outputs found

    Asymptotics of large eigenvalues for a class of band matrices

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    We investigate the asymptotic behaviour of large eigenvalues for a class of finite difference self-adjoint operators with compact resolvent in l2l^2

    Molecular portrait of chronic joint diseases: Defining endotypes toward personalized medicine.

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    Joint diseases affect hundreds of millions of people worldwide, and their prevalence is constantly increasing. To date, despite recent advances in the development of therapeutic options for most rheumatic conditions, a significant proportion of patients still lack efficient disease management, considerably impacting their quality of life. Through the spectrum of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA) as quintessential and common rheumatic diseases, this review first provides an overview of their epidemiological and clinical features before exploring how the better definition of clinical phenotypes has helped their clinical management. It then discusses the recent progress in understanding the diversity of endotypes underlying disease phenotypes. Finally, this review highlights the current challenges of implementing molecular endotypes towards the personalized management of RA, PsA and OA patients in the future

    The DAG1 transcription factor negatively regulates the seed-to-seedling transition in Arabidopsis acting on ABA and GA levels

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    BACKGROUND: In seeds, the transition from dormancy to germination is regulated by abscisic acid (ABA) and gibberellins (GAs), and involves chromatin remodelling. Particularly, the repressive mark H3K27 trimethylation (H3K27me3) has been shown to target many master regulators of this transition. DAG1 (DOF AFFECTING GERMINATION1), is a negative regulator of seed germination in Arabidopsis, and directly represses the GA biosynthetic gene GA3ox1 (gibberellin 3-β-dioxygenase 1). We set to investigate the role of DAG1 in seed dormancy and maturation with respect to epigenetic and hormonal control. RESULTS: We show that DAG1 expression is controlled at the epigenetic level through the H3K27me3 mark during the seed-to-seedling transition, and that DAG1 directly represses also the ABA catabolic gene CYP707A2; consistently, the ABA level is lower while the GA level is higher in dag1 mutant seeds. Furthermore, both DAG1 expression and protein stability are controlled by GAs. CONCLUSIONS: Our results point to DAG1 as a key player in the control of the developmental switch between seed dormancy and germination

    Legendrian Distributions with Applications to Poincar\'e Series

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    Let XX be a compact Kahler manifold and LXL\to X a quantizing holomorphic Hermitian line bundle. To immersed Lagrangian submanifolds Λ\Lambda of XX satisfying a Bohr-Sommerfeld condition we associate sequences {Λ,k}k=1\{ |\Lambda, k\rangle \}_{k=1}^\infty, where k\forall k Λ,k|\Lambda, k\rangle is a holomorphic section of LkL^{\otimes k}. The terms in each sequence concentrate on Λ\Lambda, and a sequence itself has a symbol which is a half-form, σ\sigma, on Λ\Lambda. We prove estimates, as kk\to\infty, of the norm squares Λ,kΛ,k\langle \Lambda, k|\Lambda, k\rangle in terms of Λσσ\int_\Lambda \sigma\overline{\sigma}. More generally, we show that if Λ1\Lambda_1 and Λ2\Lambda_2 are two Bohr-Sommerfeld Lagrangian submanifolds intersecting cleanly, the inner products Λ1,kΛ2,k\langle\Lambda_1, k|\Lambda_2, k\rangle have an asymptotic expansion as kk\to\infty, the leading coefficient being an integral over the intersection Λ1Λ2\Lambda_1\cap\Lambda_2. Our construction is a quantization scheme of Bohr-Sommerfeld Lagrangian submanifolds of XX. We prove that the Poincar\'e series on hyperbolic surfaces are a particular case, and therefore obtain estimates of their norms and inner products.Comment: 41 pages, LaTe

    Scattering Theory for Jacobi Operators with Steplike Quasi-Periodic Background

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    We develop direct and inverse scattering theory for Jacobi operators with steplike quasi-periodic finite-gap background in the same isospectral class. We derive the corresponding Gel'fand-Levitan-Marchenko equation and find minimal scattering data which determine the perturbed operator uniquely. In addition, we show how the transmission coefficients can be reconstructed from the eigenvalues and one of the reflection coefficients.Comment: 14 page

    Szeg\"o kernel asymptotics and Morse inequalities on CR manifolds

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    We consider an abstract compact orientable Cauchy-Riemann manifold endowed with a Cauchy-Riemann complex line bundle. We assume that the manifold satisfies condition Y(q) everywhere. In this paper we obtain a scaling upper-bound for the Szeg\"o kernel on (0, q)-forms with values in the high tensor powers of the line bundle. This gives after integration weak Morse inequalities, analogues of the holomorphic Morse inequalities of Demailly. By a refined spectral analysis we obtain also strong Morse inequalities which we apply to the embedding of some convex-concave manifolds.Comment: 40 pages, the constants in Theorems 1.1-1.8 have been modified by a multiplicative constant 1/2 ; v.2 is a final updat

    The density of stationary points in a high-dimensional random energy landscape and the onset of glassy behaviour

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    We calculate the density of stationary points and minima of a N1N\gg 1 dimensional Gaussian energy landscape. We use it to show that the point of zero-temperature replica symmetry breaking in the equilibrium statistical mechanics of a particle placed in such a landscape in a spherical box of size L=RNL=R\sqrt{N} corresponds to the onset of exponential in NN growth of the cumulative number of stationary points, but not necessarily the minima. For finite temperatures we construct a simple variational upper bound on the true free energy of the R=R=\infty version of the problem and show that this approximation is able to recover the position of the whole de-Almeida-Thouless line.Comment: a revised and shortened version with a few typos corrected and references added. To appear in JETP Letter

    Field cooling memory effect in Bi2212 and Bi2223 single crystals

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    A memory effect in the Josephson vortex system created by magnetic field in the highly anisotropic superconductors Bi2212 and Bi2223 is demonstrated using microwave power absorption. This surprising effect appears despite a very low viscosity of Josephson vortices compared to Abrikosov vortices. The superconductor is field cooled in DC magnetic field H_{m} oriented parallel to the CuO planes through the critical temperature T_{c} down to 4K, with subsequent reduction of the field to zero and again above H_{m}. Large microwave power absorption signal is observed at a magnetic field just above the cooling field clearly indicating a memory effect. The dependence of the signal on deviation of magnetic field from H_{m} is the same for a wide range of H_{m} from 0.15T to 1.7T

    On perturbations of Dirac operators with variable magnetic field of constant direction

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    We carry out the spectral analysis of matrix valued perturbations of 3-dimensional Dirac operators with variable magnetic field of constant direction. Under suitable assumptions on the magnetic field and on the pertubations, we obtain a limiting absorption principle, we prove the absence of singular continuous spectrum in certain intervals and state properties of the point spectrum. Various situations, for example when the magnetic field is constant, periodic or diverging at infinity, are covered. The importance of an internal-type operator (a 2-dimensional Dirac operator) is also revealed in our study. The proofs rely on commutator methods.Comment: 12 page

    IL-1 beta and TNF alpha Promote Monocyte Viability through the Induction of GM-CSF Expression by Rheumatoid Arthritis Synovial Fibroblasts

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    Background. Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype. Methods. SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry. Results. Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone . This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF . Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype. Conclusion. Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization
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